Process for the dehydration of substituted 4-dimethylamino-2-aryl-butan-2-ol compounds and process for the preparation of substituted dimethyl-(3-aryl-butyl)-amine compounds by heterogeneous catalysis

Abstract

Process for the preparation of substituted dimethyl-(3-aryl-butyl)-amine compounds. The process comprises dehydration by heterogeneous catalysis of substituted 4-dimethylamino-2-aryl-butan-2-ol compounds, to form substituted dimethyl-(3-aryl-but-3-enyl)-amine intermediates, which are then converted by hydrogenation with hydrogen to substituted dimethyl-(3-aryl-butyl)-amine compounds.

The invention claimed is: 
     
       1. A method for converting a compound of Formula I 
       
         
           
           
               
               
           
         
         wherein 
         R 1  represents H or C 1-5 -alkyl, 
         R 1′  represents H or C 1-5 -alkyl, 
         R 2  represents H or C 1-5 -alkyl, 
         R 3  represents H or C 1-5 -alkyl, 
         R 4 , R 4′ , R 5 , R 5′ , R 6 , which may be identical or different, each represents H, OH, C 1-4 -alkyl, OC 1-4 -alkyl, partially fluorinated or perfluorinated C 1-4 -alkyl, partially fluorinated or perfluorinated O—C 1-4 -alkyl, O—(CH 2 ) n -phenyl where n=1, 2 or 3, F, Cl or OR 8 , 
         or two adjacent radicals R 4  and R 5 , R 5  and R 6 , R 6  and R 5′  or R 5′  and R 4′  represent a group —OCH═CHO—, —CH═C(R 9 )—O—, —CH═C(R 9 )—S— or —CH═CH—C(OR 10 )═CH— as part of a ring, with the proviso that the other radicals in each case R 6 , R 5′  and R 4′ ; R 4 , R 5′  and R 6′ ; R 4 , R 5  and R 4′  or R 4 , R 5  and R 6  are as defined above, 
         R 8  represents CO—C 1-5 -alkyl, PO(O—C 1-4 -alkyl) 2 , CO—C 6 H 4 —R 11 , CO(O—C 1-5 -alkyl), CO—CHR 12 —NHR 13 , CO—NH—C 6 H 3 —(R 14 ) 2  or an unsubstituted or substituted pyridyl, thienyl, thiazoyl or phenyl group, 
         R 9  represents H or C 1-4 -alkyl, 
         R 10  represents H or C 1-3 -alkyl, 
         R 11  represents OC(O)—C 1-3 -alkyl in the ortho-position or —CH 2 —N—(R 15 ) 2  in the meta- or para-position, where R 15  in each case represents C 1-4 -alkyl or the two radicals R 15 , together with the bridging nitrogen atom, form a 4-morpholino radical, 
         R 12  and R 13 , which may be identical or different, each represents H, C 1-6 -alkyl or C 3-8 -cycloalkyl, or R 12  and R 13  together represent —(CH 2 ) 3-8  as part of a ring, 
         R 14  represents H, OH, C 1-7 -alkyl, partially fluorinated or perfluorinated C 1-7 -alkyl, OC 1-7 -alkyl, phenyl, O-aryl, F or Cl, with the proviso that the radicals R 14  are identical or different, 
         wherein in each case the compound of Formula I is in the form of one of its pure stereoisomers, a racemate, or in the form of a mixture of stereoisomers, in any desired mixing ratio, or in each case in the form of a physiologically acceptable salt, or in each case in the form of a solvate, comprising dehydrating the compound of Formula I via catalysis carried out in the presence of a polyfunctional heterogeneous catalyst to form a compound of Formula II 
       
       
         
           
           
               
               
           
         
         wherein R 1 , R 1′ , R 2 , R 3 , R 4 , R 4′ , R 5 , R 5′  and R 6  are as defined above, in each case in the form of one of its pure stereoisomers, a racemate, or a mixture of stereoisomers, in any desired mixing ratio, or in each case in the form of a physiologically acceptable salt, or in each case in the form of a solvate. 
       
     
     
       2. The method according to  claim 1 , wherein the stereoisomer of the compound of Formula I or Formula II is an enantiomer or a diastereoisomer. 
     
     
       3. The method according to  claim 1 , wherein the polyfunctional heterogeneous catalyst is at least one acidic catalyst comprising ion-exchange resins, zeolites, heteropoly acids, phosphates, and sulfates, or at least one basic catalyst. 
     
     
       4. The method according to  claim 3 , wherein the acidic catalyst further comprises at least one metal oxide including SiO 2 , Al 2 O 3 , TiO 2 , Nb 2 O 5 , B 2 O 3 , a mixture of Nb 2 O 5  and B 2 O 3 , a mixture of Al 2 O 3  and SiO 2 , or a mixture of Al 2 O 3  and B 2 O 3 , wherein said metal oxide is mixed with the component selected from the group consisting of ion-exchange resins, zeolites, heteropoly acids, phosphates, or sulfates. 
     
     
       5. The method according to  claim 4 , wherein the ion-exchange resins comprise sulfonic acid groups. 
     
     
       6. The method according to  claim 4 , wherein the ion-exchange resins are based on at least one tetrafluoroethylene/perfluorovinyl ether copolymer or at least one styrene/divinylbenzene copolymer.